Search PubMed⌕ Search

Biomedical subjects

S Takano

Publications and source records attributed to S Takano.

At least 127 records · Page 7Linked to original sources
PubMed1994

Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.

Suramin, an anticancer agent in current clinical trials, is a prototype of a pharmacological antagonist of growth factors, including basic fibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of heparin stimulated angiogenesis and counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC50) of suramin was determined for key cellular mechanisms that regulate angiogenesis: (a) low and high affinity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC50s, respectively, of 24.3 and 71.5 micrograms/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine aortic endothelial cells with IC50s of 200-320 micrograms/ml; (c) proliferation of bovine pulmonary artery endothelial cells at > 100 micrograms/ml and of BCE cells at > 250 micrograms/ml; and (d) urokinase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211 micrograms/ml and of BCE cells stimulated by bFGF at > 100 micrograms/ml, but not plasminogen activator activity induced by phorbol 12-myristate 13-acetate. Suramin inhibited multiple control points of angiogenesis, including those stimulated by bFGF. Because tumor growth is angiogenesis dependent, the clinical efficacy of suramin may relate, in part, to angiosuppression.

Animals↗
PubMed1994

Effects of thromboxane A2 agonist STA2 on rapidly adapting pulmonary stretch receptors in vagotomized rabbits.

We investigated the responses of rapidly adapting pulmonary stretch receptors (RARs) and tracheal pressure (PT) to right atrial injections of the thromboxane A2 (TXA2) stable analogue STA2 (0.3, 1.0, and 3.0 microgram/kg) before and after administration of atropine sulfate (1 mg/kg), isoprenaline (200 micrograms/kg), indomethacin (1 mg/kg), or S-145 (0.5 mg/kg) in artificially ventilated, bilaterally vagotomized rabbits. The RARs increased their activity after STA2 administration, and the increase was dose-dependent. However, intraatrial injections of STA2 at all the doses examined had no significant effect on PT. The excitatory responses of RAR activity to STA2 (0.3-3.0 micrograms/kg) were not significantly altered by administration of atropine sulfate (anticholinergic agent), isoprenaline (bronchodilator), or indomethacin (cyclooxygenase inhibitor). However, S-145 treatment (TXA2 antagonist) blocked the STA2-induced RAR stimulation. To determine whether or not administration of STA2 causes release of acetylcholine (ACh), we also examined the effects of vagal efferent stimulation (10-15 V, 10 Hz, 1 ms), STA2 administration (3.0 micrograms/kg), and their combination on PT in rabbits associated with both artificial ventilation and bilateral vagotomy. The vagally mediated bronchoconstriction that led to an increase in PT was not enhanced by simultaneous administration of STA2 at 3.0 micrograms/kg in all of the tested animals. These results suggest that the stimulation of RARs by STA2 is not mediated by the release of ACh from the nerve endings but is probably due to a local inflammatory bronchoconstriction that does not significantly alter the value of PT.

Animals↗
PubMed1994

Suramin inhibits glioma cell proliferation in vitro and in the brain.

Suramin is a novel anticancer agent that blocks the binding of growth factors, including basic fibroblast growth factor (bFGF), to their receptors. Prior studies showed human and experimental gliomas to upregulate and respond to autocrine stimulation by bFGF, the antiproliferative effects of suramin were therefore studied on glioma cell turnover in vitro and in the brain. Suramin inhibited the growth of rat (C6, 9L) and human (U-118, U-138, A-172, T98G) glioma cell lines in a dose-dependent manner. Suramin significantly reduced the bromodeoxyuridine (BUdR) labeling index of cultured glioma cells at 250 micrograms/ml, P < 0.0001. DNA flow cytometry revealed a significant decrease in the percentage of suramin-treated glioma cells in S-phase, P < 0.01. Using intracerebral rat C6 glioma model in vivo, suramin, 10-60 mg/kg, i.p., produced a dose-dependent reduction of BUdR labeling in both the glioma and endothelial cell subpopulations. Suramin, 200 mg/kg i.v., however, led to intratumoral hemorrhages that reduced survival. Electron microscopy revealed membranous inclusion bodies in the cytoplasm of C6 glioma and endothelial cells, an indication of excess glycosaminoglycans. Moreover, 46% of endothelial cells within the C6 glioma tumor treated with suramin, 60 mg/kg, i.p., developed membrane blebs. Suramin, in clinically relevant doses, significantly inhibits glioma cell growth and cytokinetics. The risk of intratumoral hemorrhage, possibly related to injury of endothelial cells or the accumulation of anticoagulant glycosaminoglycans, constitutes a major side effect and caution should be exercised in consideration of clinical application for intracerebral tumors.

Animals↗
PubMed1994

Prospective assessment of incidence of fulminant hepatitis in post-transfusion hepatitis: a study of 504 cases.

The incidence of posttransfusion hepatitis and "fulminant" hepatitis was investigated by a plan devised at our hospital in December 1982. Of 2959 blood recipients between January 1982 and December 1988, 504 (22.5%) developed posttransfusion hepatitis, with a mean transfusion volume of 10.2 units. Of the 504 cases of posttransfusion hepatitis, "icteric" (T-Bil > 2.0 mg/dl) and "overt icteric" hepatitis (T-Bil > 5.0 mg-dl) developed in 111 cases (22.0%) and 28 cases (5.6%), respectively. Of the 28 overt icteric hepatitis cases, 13 (2.8%) were thought to be true overt icteric posttransfusion hepatitis because the icterus was caused by other reasons in the other 15 cases (seven neonatal jaundice, four hemolytic anemia, one radiation hepatitis, one halothane-induced hepatitis; two other cases were excluded because chronic liver disease was diagnosed by imaging procedures despite serum ALTs in the normal range before transfusion). The anti-HCV serostatus was investigated in five of the 13 true overt icteric posttransfusion hepatitis patients using blood specimens taken 180 days or more following the onset of posttransfusion hepatitis. Anti-HCV seroconversion occurred in three of the five cases (60%). HCV seroconversions were not seen in the cases in which the icterus was due to other reasons.

Alanine Transaminase↗
PubMed1994

Effects of interferon beta on non-A, non-B acute hepatitis: a prospective, randomized, controlled-dose study. Japan Acute Hepatitis Cooperative Study Group.

BACKGROUND/AIMS: Non-A, non-B acute hepatitis progresses to a higher incidence of chronicity and hepatocellular carcinoma. To avoid the development of chronic liver disease, resolution of acute hepatitis C might be most effective. The aim was to establish the effect of interferon in disturbing progression to chronicity and to determine the most appropriate treatment protocol. METHODS: Ninety-seven acute non-A, non-B hepatitis cases were randomly assigned to six different protocols and treated with 8.4-336 MU of interferon; 90 cases were finally completely analyzed. Titers of hepatitis C virus (HCV) RNA and HCV genotypes were determined. RESULTS: Seventy-four cases were positive for second-generation anti-HCV. Of these, 65 (89%) were positive for HCV RNA. In these 65 cases, the resolution rate was 32%, and this rate was dependent on the total treatment dosage. Only the group treated with 336 MU showed a high (83%; 10/12) resolution rate; the other five groups had 0%-38% resolution. CONCLUSIONS: Interferon treatment for acute hepatitis C could be regarded as a "vaccinelike" therapy by preventing the development of the virus carrier state.

Adult↗
PubMed1994

Plasma thrombomodulin as a marker of vascular injuries in collagen vascular diseases.

Thrombomodulin, a thrombin receptor on the vascular endothelial cell surface, is released into circulating blood. The plasma concentrations in patients with collagen vascular diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, polymyositis and/or dermatomyositis (PM/DM), Behçet's disease, and Wegener's granulomatosis, were measured and compared with those of healthy persons. The mean plasma thrombomodulin concentrations in patients with juvenile rheumatoid arthritis, systemic sclerosis, PM/DM, Wegener's granulomatosis, and active states of SLE, rheumatoid arthritis, and Beçhet's disease were significantly higher than those in the control group. Patients with Wegener's granulomatosis showed the highest mean value. The mean values in patients with inactive states of the diseases and Sjögren's syndrome were not significantly different from the values in the control group. In cases of juvenile rheumatoid arthritis, systemic sclerosis, PM/DM, and Wegener's granulomatosis, patients with active interstitial pneumonitis or extensive pulmonary lesions frequently showed higher values of plasma thrombomodulin than those without overt pulmonary involvement. Elevated plasma thrombomodulin values were decreased along with amelioration of the diseases by treatment. These results may indicate that plasma thrombomodulin measurement may be helpful for evaluating vascular injury in patients with collagen diseases.

Adult↗
PubMed1994

Cortical reflex negative myoclonus.

Three patients with progressive myoclonic epilepsy (PME), two of them clinically manifesting only negative myoclonus and the other manifesting both positive and negative myoclonus, were electrophysiologically investigated, and compared with two other patients with PME presenting with only positive myoclonus. Electric stimulation of the median nerve during sustained active wrist extension in the three patients with negative myoclonus often elicited a short lapse of the posture in the stimulated hand associated with a silent period in the muscle discharge with or without being preceded by an abrupt increase in the muscle discharge (C reflex). The occurrence of the stimulus-induced silent period was significantly correlated with that of the giant somatosensory evoked potentials (SEPs), and in two patients the silent period was elicited also in the opposite (non-stimulated) hand when the giant SEP was recorded at the hemisphere ipsilateral to the stimulus as well. In one patient, the duration of the silent period was positively correlated with the amplitude of the cortical SEP. Furthermore, the duration of the induced silent period was closely related to the recovery function of SEP in each individual case. In contrast, in the two patients manifesting only positive myoclonus, the silent period was not elicited by the peripheral stimulation, and the somatosensory cortex was hyperexcitable immediately after the peripheral stimulus. Thus, this stimulus-sensitive negative myoclonus is mediated by a transcortical reflex mechanism, and corresponds to the negative form of the cortical reflex myoclonus ('cortical reflex negative myoclonus').

Adult↗
PubMed1994

Ultrastructural study of the effects of stress on the pancreas in rats.

We studied morphologic changes in a rat model of acute hemorrhagic pancreatitis in order to investigate the mechanism by which water immersion stress injures the pancreas. Acute hemorrhagic pancreatitis was induced by two intraperitoneal injections of 40 micrograms/kg body weight of caerulein at 1-h intervals under water immersion stress for 5 h at 23 degrees C. Light microscopy showed interstitial edema with inflammatory cell infiltration, degeneration and necrosis of acinar cells, and bleeding. Electron microscopy showed large autophagic vacuoles, decreased zymogen granules, and dilated rough endoplasmic reticulum in acinar cells. Basolateral exocytosis of large vacuoles and phagocytosis of the degenerated acinar cells were observed. In addition, microvascular damage, including the destruction of the capillary endothelial cells, capillary thrombosis, and the extravasation of blood cells, was seen. In contrast, in a pancreatitis model induced by caerulein injection alone, there was no bleeding, no remarkable vascular change, and no thrombosis. Degeneration and necrosis of acinar cells were less severe. In the pancreas under stress alone, microvascular damage and degeneration of acinar cells were observed. These findings demonstrate that stress injures the pancreas and worsens the pancreatitis by causing microcirculatory disturbances, such as vascular damage, thrombosis, increased vascular permeability, and bleeding. These results suggest that chemical mediators, such as free radicals and platelet-activating factor (PAF), which are produced by vascular damage and thrombosis, may accelerate the activation of zymogen proteases in acinar cells in caerulein-induced pancreatitis, leading to hemorrhagic pancreatitis.

Acute Disease↗
PubMed1994

High-yield induction of uterine endometrial adenocarcinomas in Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine via the vagina.

A total of 130 female Donryu rats (10-week-old) were divided into two groups; 80 animals in the experimental group were given a single intra-uterine administration of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina without laparotomy, and 50 animals in the control group received PEG alone in the same manner. Small numbers of animals in both groups were killed at 3, 6, 9 and 12 months after ENNG treatment for sequential histological and endocrinological examination, and at 12.5 experimental months (15 months of age) all survivors were killed. At the termination, endometrial adenocarcinomas were present in 49% of the experimental group, compared to 0% in the control group. Severe endometrial hyperplasias were also found only in the experimental group and sequential histological examination showed first appearance of hyperplasia at 6 months and adenocarcinoma at 9 months. No tumors other than uterine carcinomas were induced by ENNG and the carcinogen treatment did not affect the endocrine environment of rats, persistent estrus appearing at 6 months after the start and increasing with age in both groups. The estradiol-17 beta:progesterone (E:P) ratio was also increased after 6 months, with further elevation at 12 months to about 8 times higher than the level at 6 months. These results indicate that an increased E:P ratio might act as a promoter of development of endometrial proliferative lesions initiated by ENNG in this rat strain. The study indicates that the present simple method using Donryu rats provides a good animal model for endometrial adenocarcinoma development in women.

Adenocarcinoma↗
PubMed1994

A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepatitis C.

The effect of ursodeoxycholic acid on liver function tests and on bile acid metabolism was investigated in a multi-center randomized controlled dose study for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600 and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum liver parameters and bile acid composition in the treatment groups were compared with 17 control patients. A similarly significant decrease of serum alanine aminotransferase and serum gamma-glutamyltransferase was observed in patients administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition was determined by high-performance liquid chromatography. At entry, the relative proportions of major bile acids were similar to those observed in normal individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30 mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600 and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic acid increased in a dose-dependent manner, and it was significantly higher than in controls (p < 0.001). The hydrophobicity index of bile acids was calculated by the method of Heuman, and its correlation with serum parameter levels was analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase decreased in the cases in which hydrophobicity index significantly decreased during treatment. The same correlation was observed between the hydrophobicity index and serum gamma = glutamyltransferase in these two groups. There was no correlation between these parameters in the control and 150-mg groups. There was no correlation between reduction rate of serum alanine aminotransferase and initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

A diaminoantraquinone inhibitor of angiogenesis.

Tumor growth is dependent upon angiogenesis. There is an intense search for pharmacological inhibitors of angiogenesis as a novel approach to treat angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of compounds, originally studied as potential protein kinase C inhibitors, included the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]-4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097), was found to reversibly inhibit bovine endothelial cell growth with an IC50 that ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell migration, particularly endothelial cells stimulated by the potent angiogenic molecule, basic fibroblast growth factor. The activity of secreted urokinase-type plasminogen activator and active interstitial collagenase, but not gelatinase, was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by NSC 639366 by using the chick chorioallantoic membrane or the rat corneal bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth. These experiments introduce a novel compound that could be clinically useful against angiogenic diseases and encourage further development of compounds that inhibit the plasminogen-plasmin system known to be a key regulator of angiogenesis.

Animals↗
PubMed1994

[Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression].

A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression.

Adenocarcinoma↗
PubMed1994

[Blood concentrations of thrombomodulin in patients with various diseases].

Concentrations of thrombomodulin in blood plasma were measured by a one-step sandwich enzyme immunoassay (EIA). The concentrations in normal healthy subjects were 9.9 +/- 2.9 ng/ml. The concentrations were found to be significantly higher in patients with SLE, RA and other collagen diseases in their active stages than at their non-active stages. The concentrations increased in patients with DIC, and significantly higher levels were observed when DIC was complicated by multiple organ failure. These findings indicate that plasma concentrations of thrombomodulin may be a useful parameter for vascular injuries caused by inflammatory processes or coagulation/fibrinolysis reactions.

Adult↗
PubMed1994

[The significance of portal infusion chemotherapy for prevention of recurrence in residual liver after hepatectomy for metastases from colorectal cancer].

We performed portal infusion chemotherapy using a reservoir for prevention of recurrence in residual liver after hepatectomy for metastases from colo-rectal cancer. To study the usefulness of portal infusion chemotherapy, the period from hepatectomy to recurrence in residual liver was investigated by three treatment groups for H2 cases; (a) a group of systemic chemotherapy, (b) a group of arterial infusion chemotherapy and (c) a portal infusion chemotherapy group. Treatment in (a) group was for 204 +/- 98.2 days (n = 6), in (b) group for 343.0 +/- 238.3 days (n = 8) and in (c) group for 961.0 +/- 1,172.4 days (n = 5). There was no statistically significant difference in the three groups, but (c) group had a better result in recurrence in residual liver. As for prevention of recurrence in residual liver after re-hepatectomy, there was no significant difference in the three groups, but (c) group had the longest survival.

Aged↗
PubMed1994

[Two cases of rheumatoid arthritis presenting autoimmune hepatic diseases].

We report on two cases of rheumatoid arthritis (RA) presenting autoimmune hepatic diseases. The first patient, who had been diagnosed as RA at the age of 63, was hospitalized in order to undergo surgery for total left knee replacement at the age of 69. She acquired acute serum hepatitis as a result of blood transfusion she received during the operation. Five years later, she visited our clinic suffering from polyarthritis. She was found to have hyper-alkaline phosphatase (ALP) and hyper rGTP, but no AMA. The second patient, a 60-year-old female whose onset of RA was at the age of 45, complained of general fatigue, and was admitted to the hospital because of persistent liver dysfunction. When corticosteroid was administered to these patients, ALP and rGTP levels in the first case, and AST and ALT levels in the second case were reduced to values in the normal range. ANA in the first case continued to register negative, but ANA in the second case became positive after the patient developed acute hepatitis. Both patients were found to have anti-p25 triplet liver/kidney microsome antibody. We discuss the clinical significance of this antibody.

Aged↗